Pyruvate kinase

About: Pyruvate kinase is a research topic. Over the lifetime, 5683 publications have been published within this topic receiving 180020 citations. The topic is also known as: ATP:pyruvate 2-O-phosphotransferase & phosphoenolpyruvate kinase.

Evidence for an Alternative Glycolytic Pathway in Rapidly Proliferating Cells

Abstract: Proliferating cells, including cancer cells, require altered metabolism to efficiently incorporate nutrients such as glucose into biomass. The M2 isoform of pyruvate kinase (PKM2) promotes the metabolism of glucose by aerobic glycolysis and contributes to anabolic metabolism. Paradoxically, decreased pyruvate kinase enzyme activity accompanies the expression of PKM2 in rapidly dividing cancer cells and tissues. We demonstrate that phosphoenolpyruvate (PEP), the substrate for pyruvate kinase in cells, can act as a phosphate donor in mammalian cells because PEP participates in the phosphorylation of the glycolytic enzyme phosphoglycerate mutase (PGAM1) in PKM2-expressing cells. We used mass spectrometry to show that the phosphate from PEP is transferred to the catalytic histidine (His11) on human PGAM1. This reaction occurred at physiological concentrations of PEP and produced pyruvate in the absence of PKM2 activity. The presence of histidine-phosphorylated PGAM1 correlated with the expression of PKM2 in cancer cell lines and tumor tissues. Thus, decreased pyruvate kinase activity in PKM2-expressing cells allows PEP-dependent histidine phosphorylation of PGAM1 and may provide an alternate glycolytic pathway that decouples adenosine triphosphate production from PEP-mediated phosphotransfer, allowing for the high rate of glycolysis to support the anabolic metabolism observed in many proliferating cells.

Serine is a natural ligand and allosteric activator of pyruvate kinase M2

Abstract: The M2 isoform of pyruvate kinase (PKM2) is a key glycolytic enzyme that is overexpressed in cancer cells; here, serine is shown to bind to and directly activate PKM2, and the resulting reduction in enzyme activity under serine-deprivation conditions is shown to lead to the diversion of glucose-derived carbon to promote serine biosynthesis required for cell proliferation

Gluconeogenesis and Related Aspects of Glycolysis

Abstract: PERSPECTIVES AND SUMMARy 618 GENERAL PROPERTIES OF GLUCONEOGENESIS AND GLYCOLYSIS IN THE LIVER 619 Gluconeogenesis 619 Glycolysis 619 Control Steps 620 ENZYME PROPERTIES 620 Pyruvate Carboxylase and Other Mitochondrial Involvement 620 Phosphoenolpyruvate Carboxykinase 623 Pyruvate Kinase 625 Fructose 1,6-Bisphosphatase 626 Fructose 2,6-Bisphosphatase 629 6-Phosphofructokinases 629 Glucose 6-Phosphatase 633 Glucokinase 634 THE CONTROL OF METABOLIC FLUX BY HORMONES AND OTHER EFFECTORS ...... 634 Cyclic AMP, Glucagon, and f3-Adrenergic Agents 634 Fructose 2,6-Bisphosphate 639 ex-Adrenergic Agents, Vasopressin, and Angiotensin 641 Glucocorticoids 643 Glucose 643 THE FUTILE CYCLES 644 Glucose/Glucose 6-Phosphate Cycle 644 Fructose 6-Phosphate/Fructose 1,6-Bisphosphate Cycle 646 Pyruvate/Phosphoenolpyruvate Cycle 647

The contents of adenine nucleotides, phosphagens and some glycolytic intermediates in resting muscles from vertebrates and invertebrates

Abstract: The lowest contents of ATP and the lowest ATP/AMP concentration ratios are observed in the molluscan muscles that have very low rates of energy expenditure during contraction. The highest contents of ATP are observed in the extremely aerobic insect flight muscle and the extremely anaerobic pectoral muscle of the pheasant and domestic fowl. In general, the lowest ATP/AMP concentration ratios are observed for muscle in which the variation in the rate of energy utilization is small (e.g. some molluscan muscles, heart muscle); the highest ratios are observed in muscles in which this variation is large (lobster abdominal muscle, pheasant pectoral muscle, some insect flight muscles). This finding is consistent with the proposed role of AMP and the adenylate kinase reaction in the regulation of glycolysis. However, in the flight muscle of the honey-bee the ATP/AMP ratio is very low, so that glycolysis may be regulated by factors other than the variation in AMP concentration. The variation in the contents of arginine phosphate in muscle from the invertebrates is much larger than the variation in creatine phosphate in muscle from the vertebrates. The contents of hexose monophosphates and pyruvate are, in general, higher in the muscles of vertebrates than in those of the invertebrates. The contents of phosphoenolpyruvate are similar in all the muscles investigated, except for the honey-bee in which it is about 4-10-fold higher. The mass-action ratios for the reactions catalysed by phosphoglucoisomerase and adenylate kinase are very similar to the equilibrium constants for these reactions. Further, the variation in the mass-action ratios between muscles is small. It is concluded that these enzymes catalyse reactions close to equilibrium. However, the mass-action ratios for the reactions catalysed by phosphofructokinase and pyruvate kinase are much smaller than the equilibrium constants. The variation in the ratios between different muscles is large. It is concluded that these enzymes catalyse nonequilibrium reactions. Since the variation in the mass-action ratios for the reactions catalysed by the phosphagen kinases (i.e. creatine and arginine phosphokinases) is small, it is suggested that these reactions are close to equilibrium.